The distribution and metabolism of radiolabeled fenvalerate were compared in pyrethroid resistant (R) and susceptible (S) house flies. At the S-LD 30, there were significant differences between strains with regard to the penetration and distribution of fenvalerate and excretion of its metabolites. Penetration was faster is S resulting in two to three times higher internal levels of radiocarbon. Excretion of fenvalerate metabolites began 24 hr post-treatment in S. It began after 4 hr in R and continued in a steady state so that at 24 hr almost 50% of the topically applied dose had passed through the insect. Metabolism studies were conducted at doses (LD 5) that affected but did not kill individuals of either strain. Using thin-layer chromatography and [ 14C]fenvalerate radiolabeled in either the alcohol or acid moiety of the molecule, seven metabolites were isolated and identified from the water-soluble internal fraction and the excrement in R and S. In addition, three alcohollabeled unknowns were isolated from acid-, glucosidase-, and sulfatase-treated fly excrement. Two of the unidentified metabolites were common to both strains of flies while one was isolated only from the acid-treated excrement of R. While there were no qualitative differences in identified metabolites between strains, there were quantitative differences. Since metabolism studies with R were done at a nine-fold higher treatment dose than S, R flies metabolized as much as eight times more fenvalerate than S. Piperonyl butoxide (PBO) was an effective synergist of fenvalerate in R flies. At least two times more internal fenvalerate and approximately two times less hydroxylated metabolites were detected in R flies treated with fenvalerate-PBO (1:1) than in R flies treated with an equivalent dose of fenvalerate alone. The effect of PBO on metabolism implicates a role for the mixed-function oxidase system in the resistance mechanism of this strain of house fly.